Two years ago we began our studies on the effect of the gut using the technique of TPN (total parenteral nutrition). The work outlined in the progress report represents the first systematic assessment of the effects of the absence of food from the gut on the structural and functional integrity of the digestive tract in well-nourished animals. We have made basic observations of the role of the presence of food on secretion, motility, endocrinology, growth and immunology of the gut. During the next 4 years we propose to extend these observations and elucidate the mechanisms involved. We plan to identify the chemical constituents in a diet which are responsible for maintenance of endogenous gastrin levels and GI structure and foundation. We will examine the importance of the time a stimulant is exposed to the antral mucosa to its ability to release gastrin. We have evidence that intraluminal gastrin stimulates mucosal growth and will determine whether or not this is physiologically significant. We will determine the role of gastrin and bulk in the diet in maintaining colonic mucosal structure. Cholecystokinin will be administered to rats on TPN to determine if it will prevent pancreatic atrophy. We will also elucidate the significance of increased serum secretion levels during TPN. In addition we plan to complete our studies of the effects of TPN on hormone levels and gastric secretion in human patients.